PURKINJE-CELL LOSS IN HETEROZYGOUS STAGGERER MUTANT MICE DURING AGING

The cerebellum of the heterozygous (+/sg) staggerer mutant mouse has r ecently been proposed as a model system in which to study the genetic contribution to the normal process of central nervous system aging sin ce there is significant loss of neurons from 3 to 12 months of age (Sh ojaeian-Zanjani, H., Mariani, J., Delhaye-Bouchaud, N., and Herrup, K. (1992) Dev. Brain Res., 67, 153-160). In the current study we extend our analysis of the changes in Purkinje cell numbers up to 24 months o f age in +/sg and C57BL/6J wild-type mice. At 13 and 18 months, while wild-type Purkinje cell numbers remain unchanged, there is a 22-26% lo ss in the number of Purkinje cells in +/sg after which no further cell loss is observed. Between 18 and 24 months, however, a 22% loss of Pu rkinje cell occurs in +/+ animals, with the result that by 2 years of age, the size of the Purkinje cell population is again similar in both genotypes. Analysis of the cell loss in both the mediolateral and the anteroposterior dimensions, as well as the immunostaining of Purkinje cells in frontal sections, reveal no obvious regional variation in th e Purkinje cell loss. These results suggest that in +/sg, a precocious process of aging affects the size of the Purkinje cell population.